Reactome | SLC16A1:BSG cotransports monocarboxylates, H+ from extracellular region to cytosol

SLC16A1:BSG cotransports monocarboxylates, H+ from extracellular region to cytosol

Stable Identifier

R-HSA-9645220

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol, extracellular region

Synonyms

MCTs mediate proton-coupled transport of monocarboxylates and ketone bodies

ReviewStatus

5/5

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SLC16A1:BSG cotransports monocarboxylates, H+ from extracellular region to cytosol

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Four members of the SLC16A gene family encode classical monocarboxylate transporters, MCT1-4. They all function as proton-dependent transporters of monocarboxylic acids such as lactate and pyruvate and ketone bodies such as acetacetate and beta-hydroxybutyrate. These processes are crucial in the regulation of energy metabolism and acid-base homeostasis.

SLC16A1 encodes MCT1, a ubiquitiously expressed protein (Garcia et al. 1994). Defects in SLC16A1 are the cause of symptomatic deficiency in lactate transport (SDLT), resulting in an acidic intracellular environment and muscle degeneration (Merezhinskaya et al. 2000). Activating promotor mutations in SLC16A1 are associated with exercise-induced hyperinsulinism (EIHI), a dominantly inherited hypoglycemic disorder characterized by inappropriate insulin secretion during anaerobic exercise or on pyruvate load (Otonkoski et al. 2000). MCT1 requires the binding of a single transmembrane glycoprotein (basigin, BSG) for activity (Neuhoff et al, 2005; Halestrap 2013).

Higher uptake of dissolved acetylsalicylate (ASA-) versus neutral acid shows there are transmembrane transport processes specific to ASA- or similar ions (Leonards, 1963). For salicylate, experiments with monolayers of Caco-2 cells have shown a mixture of pH-dependent passive and active influx, and one of the participating transport proteins is SLC16A1 (MCT1) (Koljonen et al, 2008). Based on this observation, it is likely that SLC16A1 also transports ASA-.

Literature References

PubMed ID	Title	Journal	Year
15911216	pH-Dependent passive and active transport of acidic drugs across Caco-2 cell monolayers Neuhoff, S, Ungell, AL, Zamora, I, Artursson, P	Eur J Pharm Sci	2005
8124722	Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle Garcia, CK, Goldstein, JL, Pathak, RK, Anderson, RG, Brown, MS	Cell	1994
18582575	Transport evaluation of salicylic acid and structurally related compounds across Caco-2 cell monolayers and artificial PAMPA membranes Koljonen, M, Rousu, K, Cierny, J, Kaukonen, AM, Hirvonen, J	Eur J Pharm Biopharm	2008
24265240	Monocarboxylic acid transport Halestrap, AP	Compr Physiol	2013
10590411	Mutations in MCT1 cDNA in patients with symptomatic deficiency in lactate transport Merezhinskaya, N, Fishbein, WN, Davis, JI, Foellmer, JW	Muscle Nerve	2000
17701893	Physical exercise-induced hypoglycemia caused by failed silencing of monocarboxylate transporter 1 in pancreatic beta cells Otonkoski, T, Jiao, H, Kaminen-Ahola, N, Tapia-Paez, I, Ullah, MS, Parton, LE, Schuit, F, Quintens, R, Sipilä, I, Mayatepek, E, Meissner, T, Halestrap, AP, Rutter, GA, Kere, J	Am J Hum Genet	2007
13929721	The influence of solubility on the rate of gastrointestinal absorption of aspirin LEONARDS, JR	Clin Pharmacol Ther	1963